We propose to continue our study of rhesus monkey models of human depressive phenomena, with our major focus on identifying the basis for and specifying the characteristics of individual differences in depressive reactions to stressors. The proposed research will be carried out in 3 phases. First, we will identify within our laboratory population of adolescent monkeys a subgroup of subjects who are at high risk for depressive reactions to stressors and a subgroup of subjects who are at low risk for such depressive reactions; the subgroups will be compared with respect to physical, social, motivational, and biochemical measures. Second, having identified high and low risk subjects, we will study in detail their reactions to a variety of stressors, including repetitive social separations, introduction into groups of strangers, and alteration of brain catecholamine metabolism via treatment with AMPT. The mildest of these stressors will elicit depressive reactions in high risk subjects, but not in low risk subjects, while the most potent combination of stressors will elicit depressive reactions in all subjects. The reactions of high and low risk subjects to these stressors will be compared on a variety of behavioral, motivational, cognitive, and biochemical measures. Finally, we will subject both high and low risk monkeys to identical protocols of tricyclic antideprssant treatment, in order to compare their respective responsiveness in terms of the same behavioral, motivational, and cognitive measures.